U.S. patent number 6,585,773 [Application Number 09/763,304] was granted by the patent office on 2003-07-01 for insertable stent and methods of making and using same.
This patent grant is currently assigned to Providence Health System-Oregon. Invention is credited to Hua Xie.
United States Patent |
6,585,773 |
Xie |
July 1, 2003 |
**Please see images for:
( Certificate of Correction ) ** |
Insertable stent and methods of making and using same
Abstract
An insertable stent is provided for joining together and
facilitating healing of adjacent tissues. Typically, the tissues
are mammalian tissues. The insertable stent is made from completely
non-toxic, bio- and blood-compatible materials. Each of the tissues
employed herein defines an internal cavity. The insertable stent
body defines a bore. The bore permits fluid to pass through the
insertable stent body. In use, the insertable stent body is
introduced into the internal cavities of the tissues. The
insertable stent body fits within the confines of, and in contact
with, each of the adjacent tissues. Typically, at least a portion
of the insertable stent body is fusible to the adjacent tissues for
facilitating healing of these tissues.
Inventors: |
Xie; Hua (Beaverton, OR) |
Assignee: |
Providence Health System-Oregon
(Seattle, WA)
|
Family
ID: |
22262954 |
Appl.
No.: |
09/763,304 |
Filed: |
February 20, 2001 |
PCT
Filed: |
August 18, 1999 |
PCT No.: |
PCT/US99/19003 |
PCT
Pub. No.: |
WO00/10488 |
PCT
Pub. Date: |
March 02, 2000 |
Current U.S.
Class: |
623/23.7;
606/213; 606/214 |
Current CPC
Class: |
A61L
31/043 (20130101); A61L 31/044 (20130101); A61L
31/046 (20130101); A61L 31/16 (20130101); A61L
31/18 (20130101); A61L 31/043 (20130101); A61L
31/18 (20130101); A61L 31/16 (20130101); A61L
31/148 (20130101); A61L 31/14 (20130101); A61L
31/046 (20130101); A61L 31/044 (20130101); A61L
31/005 (20130101); A61B 2017/00004 (20130101); A61B
2017/00508 (20130101); A61F 2/82 (20130101); A61L
2300/00 (20130101); A61B 90/39 (20160201) |
Current International
Class: |
A61L
31/14 (20060101); A61L 31/04 (20060101); A61L
31/16 (20060101); A61L 31/18 (20060101); A61F
002/04 () |
Field of
Search: |
;623/925,23.7,23.72,23.75,1.47,1.48 ;606/213,214 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Willse; David H.
Assistant Examiner: Blanco; Jamie S.
Attorney, Agent or Firm: Marger Johnson & McCollom,
P.C.
Government Interests
This invention was made with Government support under Grant No.
DAMD17-96-1-6006 awarded by U.S. Army Medical Research Acquisition
Activity. The U.S. Government has certain rights in the invention.
Parent Case Text
This application claims the benefit of Provisional Application No.
60/097,357, filed Aug. 21, 1998.
Claims
What is claimed is:
1. An insertable stent for joining together and facilitating
healing of adjacent tissues, the tissues defining an internal
cavity, the insertable stent comprising an insertable stent body
including at least one fusible portion, and at least one unfusible
portion having a portion which is dissolvable during healing
permitting fluid to pass therethrough, the insertable stent body
being introduceable into, and fitting within the confines of the
internal cavity, in contact with and fusible to the adjacent
tissues.
2. The insertable stent of claim 1, which defines a bore
therewithin for permitting fluid to pass therethrough.
3. The insertable stent of claim 1, wherein the insertable stent
body comprises a biocompatable insertable stent body.
4. The insertable stent of claim 1, wherein the insertable stent
body includes a chromophore in the fusible portion.
5. The insertable stent of claim 4, wherein said chromophore
comprises a dye material.
6. The insertable stent of claim 1, wherein the insertable stent
body includes at least one therapeutic drug.
7. The insertable stent of claim 6, wherein said therapeutic drug
is selected from the group consisting of antibiotics,
antiinflammatories, antithrombotics, vitamins, peptide growth
factors.
8. The insertable stent of claim 1, wherein the insertable stent
body comprises a protein.
9. The insertable stent of claim 8, wherein said protein is
selected from the group consisting of albumins, elastins,
collagens, globulins, fibrinogens, fibronectins, thrombins, and
fibrins.
10. The insertable stent of claim 1, wherein the fusible portion of
the insertable stent is formed employing an energy source.
11. The insertable stent of claim 10, wherein said energy source is
electromagnetic, photothermal or photochemical.
12. The insertable stent of claim 1, wherein the insertable stent
body includes a radiopaque agent.
13. The insertable stent of claim 12, wherein said radiopaque agent
is selected from the group consisting of iothalamate meglumine,
diatrizoate meglumine, diatrizoate sodium, and ioversol.
14. A method for manufacturing an insertable stent for joining
together and facilitating healing of adjacent tissues, the tissues
defining an internal cavity, comprising: forming an insertable
stent body including at least one fusible portion, and at least one
unfusible portion having a portion which is dissovable during
healing permitting fluid to pass therethrough, the insertable stent
body being introduceable into, and fitting within the confines of
the internal cavity, in contact with and fusible to the adjacent
tissues.
15. The method of claim 14, wherein the insertable stent body
defines a bore therewithin for permitting fluid to pass
therethrough.
16. The method of claim 14, wherein said insertable stent body is a
biocompatable insertable stent body.
17. The method of claim 14, which includes incorporating at least
one chromophore into said insertable stent body in the fusible
portion.
18. The method of claim 17, wherein said chromophore is a dye
material.
19. The method of claim 14, which includes incorporating at least
one therapeutic drug into said insertable stent body.
20. The method of claims 19, wherein said therapeutic drug is
selected from the group consisting of antibiotics,
antiinflammatories, antithrombotics, vitamins, peptide growth
factors.
21. The method of claim 14, wherein the insertable stent body
comprises a protein.
22. The method of claim 21, wherein said protein is selected from
the group consisting of albumins, elastins, collagens, globulins,
fibrinogens, fibronectins, thrombins and fibrins.
23. The method of claim 14, wherein the fusible portion of the
insertable stent is formed employing an enery source.
24. The method of claim 23, wherein said energy source is
electromagnetic, photothermal or photochemical.
25. The method of claim 14, wherein the insertable stent body
comprises a radiopaque agent.
26. The method of claim 25, wherein said radiopaque agent is
selected from the group consisting of iothalamate meglumine,
diatrizoate meglumine, diatrizoate sodium, and ioversol.
27. A method for joining together and facilitating healing of
tissues, comprising: providing a plurality of tissues each having
an internal cavity and ends; providing an insertable stent
comprising a insertable stent body including at least one fusible
portion, and at least one unfusible portion having a portion which
is dissolvable during said healing; introducing said insertable
stent into the internal cavity of each tissue; aligning the tissues
so that the ends are located adjacent to each other; and fusing
said fusible portion of said insertable stent body to said
tissues.
28. The method of claim 27, wherein said unfusible portion defines
a bore therewithin for permitting fluid to pass therethrough.
29. The method of claim 27, wherein the insertable stent body
comprises a biocompatable insertable stent body.
30. The method of claim 27, wherein the insertable stent body
includes a chromophore in the fusible portion.
31. The method of claim 30, wherein said chromophore is a dye
material.
32. The method of claim 27, wherein said insertable stent body
comprises a protein.
33. The method of claim 32, wherein said protein is selected from
the group consisting of alburins, elastins, collagens, globulins,
fibrinogens, fibronectins, thrombins and fibrins.
34. The method of claim 27, wherein said insertable stent body,
upon fusing, comprises a denatured portion and a non-denatured
portion.
35. The method of claim 27, wherein said fusing of insertable stent
body to tissues comprises electromagnetically radiating said
insertable stent body.
36. The method of claim 27, wherein said insertable stent body
comprises at least one fused and at least one unfused portion; and
which includes the step of dissolving at least a portion of the
unfused portion of said insertable stent body during healing of
said tissues.
37. The method of claim 27, wherein the insertable stent body
includes at least one therapeutic drug; and which includes the step
of releasing at least a portion of said therapeutic drug from the
insertable stent body during healing of said tissues.
38. The method of claim 37, wherein said therapeutic drug is
selected from the group consisting of antibiotics,
antiinflammatories, antithrombotics, vitamins, peptide growth
factors, nerve growth factors, and insulin like growth factors.
39. The method of claim 27, wherein the tissues are selected from a
group consisting of blood vessels, gastrointestinal, genitourinary,
reproductive, respiratory tubes, grafts, and synthetic
prosthetics.
40. The method of claim 27, wherein at least one of the tissues
expands when said insertable stent is introduced into said
cavity.
41. The method of claim 27, wherein fusing is conducted without the
use of an energy source which is extrinsic to the tissues.
42. The method of claim 27, wherein fusing comprises photothermal
bonding.
43. The method of claim 27, wherein fusing comprises photochemical
bonding.
44. The method of claim 27, wherein the insertable stent body
comprises a radiopaque agent.
45. The method of claim 44, wherein said radiopaque agent is
selected from the group consisting of iothalainate meglumine,
diatrizoate meglumine, diatrizoate sodium, and ioversol.
46. An insertable stent for joining together and facilitating
healing of adjacent tissues, each of the adjacent tissues defining
an internal cavity, the insertable stent comprising: an insertable
stent body, formed of a protein, including at least one fusible
portion and at least one unfusible portion, each said unfusible
portion having a portion which is dissolvable during said healing;
and said unfusible portion of the insertable stent body permitting
fluid to pass therethrough, the insertable stent body being
introduceable into, and fitting within the confines of the interal
cavity, in contact with the adjacent tissues.
Description
BACKGROUND OF THE INVENTION
The present invention relates to stent technology. Advances of
laser tissue welding in urinary tract repair are able to provide a
rapid watertight seal and avoid potential lithogenesis caused by
conventional sutures and staples. However, some problems have
limited the clinical use of this technology, such as unreliable
fusion strength, thermal damage of welded tissue and lack of a
standard reference endpoint during welding procedures.
In U.S. Pat. No. 5,549,122, a method and apparatus for molding
polymeric structures in vivo is disclosed. The structures comprise
polymers that may be heated to their molding temperature by
absorption of visible or near-visible wavelengths of light. By
providing a light source that produces radiation of the wavelength
absorbed by the polymeric material, the material may be selectively
heated and shaped in vivo without a corresponding heating of
adjacent tissues or fluids to unacceptable levels. The apparatus
comprises a catheter having a shaping element positioned near its
distal end. An emitter provided with light from at least one
optical fiber is positioned within the shaping element. The emitter
serves to provide a moldable polymeric article positioned on the
shaping element with a substantially uniform light field, thereby
allowing the article to be heated and molded at a desired treatment
site in a body lumen.
In U.S. Pat. No. 5,141,516, a dissolvable anastomosis stent
comprises a first member for receiving a first vessel stump, a
second member for receiving a second vessel stump, and engaging
means for engaging the first and second members where the engaging
means and members are constructed of a biocompatible, non-toxic
material which substantially completely dissolves mammalian bodily
fluids. In addition, methods for preparing the dissolvable
anastomosis stent and methods for surgical mammalian anastomoses
using the dissolvable anastomosis stent are disclosed.
In U.S. Pat. No. 5,306,286, an absorbable stent for placement at
the locus of a stenotic lesion which is flexible and compliance for
safe and effective delivery to the cite of a coronary obstruction,
for example, and so as to avoid arterial rupture or aneurysm
formation while under continuous stress of a beating heart. The
stent is expandable from a reduced diameter configuration, which
facilitates delivery to the cite of a targeted arterial
obstruction, to an expanded configuration when disposed within the
targeted area The stent can be carried to the cite to be treated
and expanded to its supporting diameter on any suitable expandable
catheter such as a mechanically expandable catheter or a catheter
having an inflatable balloon. The stent is formed so as to have a
wall with pores and/or holes to facilitate tissue ingrowth and
encapsulation of the stent. The stent will subsequently be
bioabsorbed to minimize the likelihood of embolization of the
dissolved material.
In U.S. Pat. No. 5,192,289, a stent or support is disclosed for use
in the connection or anastomosis of severed vessels to support and
seal the anastomotic site. The stent includes substantially
cylindrical sections separated by a tapered transitional region.
The cylindrical sections are provided with flanges that define
tapered sealing surfaces. The dimensions of the two sections are
selected to correspond with the diameter of the portions of the
vessel to be supported. The stent is preferably made of
polyglycolic acid and the dimensions of the stent are selected to
provide optimal support and sealing characteristics with a minimum
of damage to the epithelial lining of the vas deferens. In two
preferred applications, the stent is used in anastomosis of the
severed ends of a vas deferens and a Fallopian tube. A gauge is
used to measure the severed ends and, in that manner, determine the
appropriate dimensions of the stent.
In U.S. Pat. No. 5,425,739, a stent or support is disclosed for use
in the connection or anastomosis of severed vessels to support and
seal the anastomotic site. The stent includes substantially
cylindrical sections separated by a tapered transitional region.
The cylindrical sections are provided with flanges that define
tapered sealing surfaces. The dimensions of the two sections are
selected to correspond with the diameter of the portions of the
vessel to be supported. The stent is preferably made of
polyglycolic acid and the dimensions of the stent are selected to
provide optimal support and sealing characteristics with a minimum
of damage to the epithelial lining of the vas deferens. In three
preferred applications, the stent is used in anastomosis of the
severed ends of a vas deferens, a Fallopian tube, and a blood
vessel. A gauge is used to measure the severed ends and, in that
manner, determine the appropriate dimensions of the stent. A
technique of forming porous stents, and other structures, is also
disclosed.
In U.S. Pat. No. 5,662,712, a method and apparatus for molding
polymeric structures in vivo is disclosed. The structures comprise
polymers that may be heated to their molding temperature by
absorption of visible or near-visible wavelengths of light. By
providing a light source that produces radiation of the wavelength
absorbed by the polymeric material, the material may be selectively
heated and shaped in vivo without a corresponding heating of
adjacent tissues or fluids to unacceptable levels. The apparatus
comprises a catheter having a shaping element positioned near its
distal end. An emitter provided with light from at least one
optical fiber is positioned within the shaping element. The emitter
serves to provide a moldable polymeric article positioned on the
shaping element with a substantially uniform light field,
thereby
In U.S. Pat. No. 5,762,625, a luminal stent inserted and fixed in a
vessel, such as a blood vessel, so as to maintain the shape of the
vessel, and a device for inserting and fixing the luminal stent,
are disclosed. The luminal stent is formed of a yarn of
bioabsorbable polymer fibers, which yarn is shaped in a non-woven
non-knitted state in, for example, a meandering state, around the
peripheral surface of an imaginary tubular member. The
bioabsorbable polymer includes polylactic acid, polyglycol acid,
polyglactin, polydioxanone, polyglyconate, polyglycol acid and a
polylactic acid-.epsilon.-caprolactone copolymer. The device for
inserting and fixing the luminal stent consists in a catheter
having a balloon-forming portion in the vicinity of a distal end
thereof and the luminal stent fitted on the balloon-forming portion
and affixed to the balloon-forming portion by a bio-compatible
material, such as an in vivo decomposable polymer, such as
polylactic acid, water-soluble protein or fibrin sizing agent.
In U.S. Pat. No. 5,292,362, a composition is disclosed for bonding
separated tissues together or for coating tissues or prosthetic
materials including at least one natural or synthetic peptide and
at least one support material which may be activated by energy and
to methods of making and using the same.
In U.S. Pat. No. 5,527,337, a bioabsorbable stent is provided for
placement at the locus of a stenotic portion of a body passage,
such as a blood vessel, which is flexible and compliant for safe
and effective delivery to the site of the stenotic portion of, for
example, a blood vessel, and so as to avoid the disadvantages of
chronic implantation, such as arterial rupture or aneurism
formation while exposed to the continuous stresses of a beating
heart. The stent is formed from a bioabsorbable material and is
porous or has apertures defined there through to facilitate tissue
ingrowth and encapsulation of the stent. The stent is encapsulated
and biodegrades or bioabsorbs within a period of days, weeks or
months as desired following encapsulation to thereby minimize the
likelihood of embolization or other risks of the dissolved material
and to avoid the disadvantages of chronic implantation.
In U.S. Pat. No. 5,209,776, a tissue bonding and sealing
composition and method of using the same is provided. Disclosed is
a composition for bonding separated tissues together or for coating
tissues or prosthetic materials including at least one natural or
synthetic peptide and at least one support material which may be
activated by energy.
In U.S. Pat. No. 5,510,077, an intraluminal stent comprising fibrin
treatment of restenosis is provided by a two stage molding
process.
In U.S. Pat. No. 5,776,184, a device for delivery of a therapeutic
substance into a body lumen including a polymer in intimate contact
with a drug on a stent allows the drug to be retained on the stent
during expansion of the stent and also controls the administration
of drug following implantation. The adhesion of the coating and the
rate at which the drug is delivered can be controlled by the
selection of an appropriate bioabsorbable or biostable polymer and
the ratio of drug to polymer.
In U.S. Pat. No. 5,659,400, a method for making an intravascular
stent by applying to the body of a stent a solution which includes
a solvent, a polymer dissolved in the solvent and a therapeutic
substance dispersed in the solvent and then evaporating the
solvent. The inclusion of a polymer in intimate contact with a drug
on the stent allows the drug to be retained on the stent during
expansion of the stent and also controls the administration of drug
following implantation. The adhesion of the coating and the rate at
which the drug is delivered can be controlled by the selection of
an appropriate bioabsorbable or biostable polymer and the ratio of
drug to polymer in the solution. By this method, drugs such as
dexamethasone can be applied to a stent, retained on a stent during
expansion of the stent and elute at a controlled rate.
During the past decade, the application of laser solders has
greatly increased the bonding strength of laser fusion. Human
albumin as a suitable solder agent were applied in several tissue
welding such as urethra, ureters, skin and vascular due to its high
safety. Several studies have demonstrated that the welding strength
of laser tissue soldering depended on solder protein concentration.
But, the technical problem still remains is the precise
seromuscular apposition of tubular organs for accurate placement of
the laser spot and uniform layering of the solder on the fusion
surface during laser welding procedures. Those problems could cause
fusion strength unreliable, wound healing process prolonged and
increased scar tissue at anastomotic site so that anastomosis
failed.
SUMMARY OF THE INVENTION
An insertable stent is provided for joining together and
facilitating healing of adjacent tissues. Typically, the tissues
are human tissues. Preferably, the insertable stent is made from
completely non-toxic, bio- and blood-compatible materials, which
are abstracted from the native serum and tissue of mammalian.
Each of the tissues employed herein defines an internal cavity.
More preferably, the insertable stent comprises an insertable stent
body which defines a bore. The bore permits fluid to pass through
the insertable stent body.
In use, the insertable stent body is introduced into the internal
cavities of the tissues. The insertable stent body fits within the
confines of, and in contact with, each of the adjacent tissues.
Most preferably, at least a portion of the insertable stent body is
fusible to the adjacent tissues for facilitating healing of these
tissues.
The preferred insertable stent of this invention is different than
previous products in that it is made from mammalian serum and
tissue, which is completely non-toxic, bio- and blood compatible,
and is therefore substantially dissolvable. More specifically,
during the healing process, at least a portion of the insertable
stent body can be dissolved. Preferably, the insertable stent
comprises a biocompatable insertable stent body.
The insertable stent body preferably includes chromophores such
photothermal dye materials for absorbing electromagnetic radiation.
The stent typically plays support, alignment, and soldering roles
in the photothermal welding anastomosis processes. Thus
photothermal welding is simplified and quickened, and the strength
of welding is reinforced using the insertable stent. Suitable
chormophoric dyes comprise indocyanine green, methylene blue,
flourescein, and india ink, Prussian blue, copper phthalocyanine,
eosins, acridine, iron oxide, jenner stain, and acramine
yellow.
The insertable stent body preferably includes at least one
therapeutic drug. Examples of such drugs are; antibiotics such as
penicillin, ampiciline, and gentamycin; antiinflammatories such as
glucocorticoids, dexamethasone; antithombotics such as heparain;
vitamins and peptide growth factors such as epithelial growth
factor and transforming growth factor; nerve growth factors, and
insulin like growth factors.
The insertable stent body can preferably comprise a protein. For
example, the insertable stent body can comprise any one or more of
the following proteins: albumin, elastin, collagen, globulin,
fibrinogen, fibronectin, thrombin, polypeptides, and fibrins. The
insertable stent body can also comprise a carbohydrate, typically a
sugar.
The insertable stent body preferably includes a radiopaque agent
for preventing passage of x-rays or other radiation. Examples of
such agents are; iothalamate meglumine, diatrizoate meglumine,
diatrizoate sodium, and ioversol.
Furthermore, a method can also be provided for manufacturing an
insertable stent for joining together and facilitating healing of
adjacent tissues. The method preferably comprises first forming the
insertable stent body and then forming a bore therewith for
permitting fluid to pass therethrough.
In addition, a method is provided for using the insertable stent to
join together and facilitate healing of the adjacent tissues. The
method preferably comprises providing a plurality of tissues, each
having an internal cavity and ends. Then, the above described
insertable stent is introduced into the cavity of each tissue.
Finally, the tissues are aligned so that the ends are located
adjacent to each other, and the insertable stent body is fused to
the tissues. In another embodiment of the invention, the tissues
are fused to each other.
The step of fusing the insertable stent body to the adjacent
tissues preferably comprises electromagnetically radiating the
insertable stent body, which most preferably comprises a
photothermal dye such as described above. After the fusing step is
completed, preferably, the insertable stent body generally
comprises at least one fused portion and at least one unfused
portion. The method preferably includes the step of dissolving at
least a portion of the unfused portion of the insertable stent body
during healing of the tissues. More specifically, the insertable
stent could be photothermally sensitive which allows it to absorb a
range of wavelengths of a light source that produces a heat
denatured reaction to coagulate and bind tissues at irradiation
site, and which depends on what chromophores are added. The stent
can produce heat denatured coagulation reaction by other energy
sources. The stent is preferably designed so that the non-denatured
portion is dissolved in body fluid in several minutes, and the
denatured portion adheres to a bond site to form a seal circular
ring to seal and support the vessel anastomosis site so that be it
will be biodegradable during the healing process.
An insertable stent can be made from a mammalian serum and/or a
tissue source which comprises hydrolyzable protein that is a group
of non-toxic, bio- and blood-compatible natural material. The
insertable stent, including chromophores, plays a significant
support role in the vessel intralumen and plays a soldering role in
the energy welding processes. The non-denatured portion of the
stent is typically dissolved in body fluid after energy welding
anastomosis as so to not effect the vessel fluid flow and to be
biodegradable.
The insertable stent can be used for temporal connection and
supporting vessels during anastomosois processes. The anastomostic
techniques are conventionally those such as suturing, stapling,
gluing and energy welding processes.
The insertable stent with chromophores which is a photothermal
sensitive insertable stent will be used for temporal connection and
supporting vessels during end to end anastomosis techniques which
comprise several sutureless vessel anastomosis techniques using
energy welding to produce heat coagulation effect. The anastomostic
techniques consist of conventional suturing, stapling, gluing and
energy welding processes.
The stent will be as a drugs carrier to increase local drug
concentration in the intraluminal of vessel for therapeutic and
preventing the surgical complication as wound healing delayed,
stricture of anastomosis and/or diseases. The method can also
include the step of releasing at least a portion of the therapeutic
drug from the insertable stent body. This will assist with the
healing of the tissues.
The tissues are preferably selected from a group consisting of
blood vessels, gastrointestinal, genitourinary, reproductive,
respiratory tubes, grafts, and synthetic prosthetics. At least one
of the tissues will preferably expand when the insertable stent is
introduced into the cavity.
The fusing preferably comprises photothermal bonding such as laser
welding. The fusing can also comprise thermal bonding facilitated
by bipolar electrodes or magnetic and microwave thermal welding.
The fusing can also comprise chemical bonding without an energy
source which is extrinsic to the tissues, such as with
biocompatable sealants. Examples of such sealants are cyanoacrylate
glue and fibrin glue. The fusing can also comprise photochemical
bonding, such as riboflavin fusion.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is schematic view of the insertable stent according to the
present invention;
FIG. 2 is an end view taken along line 2--2 in FIG. 1;
FIG. 3 is a schematic view showing the insertable stent immediately
after introduction into tissue cavity in accordance with the
present invention;
FIG. 4 is a schematic view during the fusing procedure in
accordance with the present invention;
FIG. 5 is a schematic view after fusing and dissolving, and during
healing of the tissues in accordance with the present
invention.
FIG. 6 is a schematic view during the fusing procedure in
accordance with the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Referring to the drawings, there is shown in FIGS. 1 and 2 an
insertable stent 10 in accordance with the present invention. The
insertable stent 10 comprises an insertable stent body 12 having an
outer surface 14. The insertable stent body 12 defines a bore 16
for permitting fluid to pass therethrough. In the preferred
embodiment, the insertable stent body 12 is formed from a material
that dissolves in bodily fluids, is non-toxic, and causes little or
no inflammation in the tissues during the healing process. Most
preferably, an insertable stent body 12 formed from human serum
albumin is used. FIGS. 3-6 shows the preferred technique for using
the insertable stent body to join together and facilitate healing
of adjacent tissues. As depicted in FIG. 3, the insertable stent
body 12 is inserted into tissue cavities 22 defined by a first
tissue 18 and second tissue 20. The tissues have tissue ends 32.
Once inserted into the cavities 22, the outer surface 14 is in
contact with both first tissue 18 and second tissue 20. In one
aspect of the invention, the insertable stent body 12 stretches and
expands the tissues when it is inserted therein.
In the preferred embodiment, the insertable stent body 12 comprises
a fusible chromophore-containing insertable stent body portion 24.
The fusible dyed insertable stent body portion 24 comprises an
energy absorbing material such as a chormophore, preferably, a
photothermal dye such as indocyanine green. After the insertable
stent is inserted into the tissue cavities 22, the tissue ends 32
are aligned so that they are adjacent to each other as shown in
FIGS. 4 and 6. Next, electromagnetic radiation 30 is directed at
the fusible dyed insertable stent body portion 24. Preferably, the
electromagnetic radiation 30 has a wavelength that is not absorbed
by the tissues, but that will fuse the insertable stent body 12 to
the tissues. Most preferably, the electromagnetic radiation 30 has
a wavelength of about 800 nm. The electromagnetic radiation 30
directed at the fusible dyed insertable stent body portion 24 is
absorbed by the dye and converted into thermal energy. The thermal
energy causes the radiated portion of the fusible dyed insertable
stent body portion 24 to fuse to the tissues, thus forming the
fused insertable stent body-tissue portion 26.
Advantageously, the energy source is an electromagnetic energy
source, such as a laser, and the absorbing agent is a dye having an
absorption peak at a wavelength corresponding to that of the laser.
The biomaterial and the tissue to be welded have much less
absorption of light at this wavelength and the effect therefore is
confined to a zone around the dyelayer. A preferred energy source
is a laser diode having a dominant wavelength at about 808 nm and a
preferred dye is indocyanine green (ICG), maximum absorbance
795-805 nm. Other laser/dye combinations can also be used. It is
preferred that the dye be incorporated in the insertable stent body
portion 24. The dye can also be applied to the surface of the body
portion 24 is to be welded or secured to the tissue. The dye can be
applied directly to the body portion 24 or the surface of the body
portion 24 can first be treated or coated (eg primed) with a
composition that controls absorption of the dye into thereinto so
that the dye is kept as a discrete layer or coating.
Alternatively, the dye can be bound to the body portion 24 so that
it is secured to the surface and prevented from leeching into the
material. The dye can be applied in the form of a solution or the
dye can be dissolved in or suspended in a medium which then can be
applied as a thin sheet or film, preferably, of uniform thickness
and dye concentration.
In the preferred embodiment, once the fused insertable stent
body-tissue portion 26 has been formed, the remainder of the
insertable stent body 12 is dissolved away by the human bodily
fluids passed through the bore 16. As shown in FIG. 5, the fused
insertable stent body-tissue portion 26 bonds the tissue ends 32
together and forms a liquid tight seal during healing of the
tissues.
EXAMPLE 1
Sutureless End to End Ureteral and Heterograft Anastomosis--In
Vitro Study
Preparation of PSH Stent and Solder
25% Human serum albumin (MW: 66,500, Michigan Dept. of Public
Health, U.S. license No.99, MI) was filtered through an ultrafilter
membrane (YM 30, Amicon) using the ultrafiltration system (Model
8400, Amicon, MA) to concentrate it to 50% (W./V.). 10 mM ICG
(Sigma, I2633, MO) solution was filtered for sterilization (Gameo
25ES, Fisher) and added to 50% albumin at 1:100 by volume and mixed
well for 3 min. The mixture was air blow until the solvent
evaporated and became moldable. The moldable albumin was molded to
a hollow stent with outer diameter of 3.5 mm, inner diameter of 2.0
mm and 1.5 cm in length. The stent was stored at about -4.degree.
C. in the dark until use. The procedure was performed using sterile
techniques. The liquid solder was made of 50% (W./V.) albumin with
0.1 mM ICG that was made similar to the photothermal sensitive
stent without drying procedures. The solder was stored in a 1 ml
syringe at -4.degree. C. in the dark until use.
Elastin Based Heterograft
The elastin based heterograft was processed from freshly harvested
porcine carotid arteries. The vessels were decellularized and
digested by 1% triton-X 100, DNase and collagenase. The final
product was composed of elastin at lumen surface and collagen on
the outer surface, and each graft was 6 cm in length, 3-4 mm in
inside diameter and 1 mm thick.
Laser System
Laser treatments were performed with a diode laser module (Diomed
Limited, Cambridge, UK) coupled to a quartz silica non-contact
fiber optic (600 .mu.m diameter). The laser system consists of a
phased array of gallium-aluminum-arsenide semiconductor diodes, and
the major wavelength output of the diode laser is 808 nm. In aiming
beam allow the operator to visualize the spot size of the laser
during activation. The spot diameter was .about.1 mm at a distance
of .about.2 mm. Laser power was measured and recorded at the out of
the optic fiber with a built-in laser meter monitor. The maximum
diode power output is 25 W. The laser was used in continuous wave
mode with 1 W output.
Fresh ureter segments were harvested from domestic swine with
minimal trauma and immediately placed in sterile 0.9% saline
solution at -4.degree. C. Elastin based heterograft was provided by
our biomaterial research laboratory.
The study was divided into three groups. In group 1, 12 ureters
were completely transected and were reanastomosed end to end using
PSH stent laser fusion. In group 2, 12 ureters were anastomosed to
the elastin based heterograft using PSH stent laser fusion and in
group 3, 17 ureter to heterograft anastomosis were using laser
liquid solder technique. Each ureter or elastin based heterograft
was carefully placed over and tied on a stainless steel tube with
1-0 silk tie to prevent sliding. The stainless steel tube was
connected in parallel to an infusion pump (Syringe infusion pump
22, Harvard apparatus, MA) and pressure recorder (Pressure Monitor
4, Living System Instrumentation, VT). The ureters and heterograft
stumps were spatulated and opposed using two 6-0 vicyl sutures.
During PSH stent laser welding, the two ends were pulled over the
PSH Stent to approximate in an end to end fashion. While working on
liquid solder welding, the ureter and heterograft ends were pulled
over a 3.5 mm OD. balloon catheter for end to end apposition. The
solder was applied in a thin coat on the seam before laser welding.
The solder covered approximately 1 mm on each side of the
anastomosis. The holding suture material melted away with laser
welding. The samples were treated for burst pressure and tensile
strength testing.
A perfusion system was set up between the welded vessel and
infusion pump for burst pressure testing. A 0.9% NaCl with 1%
methylene blue solution was infused at 2 ml/min flow rate to
dissolve the PSH stent and check up for leaks of anastomotic site.
After the stent was dissolved, the pressure recorder switch was
turned on to record welding burst pressure. The expandable balloon
catheter was deflated and removed carefully from welded vessel
using laser welding.
The vessels were perfused for an hour and then the burst pressure
(mmHg) was recorded. While the vessel didn't break during the burst
pressure testing were sent for histological examination.
The welded vessels were soaked in 37.degree. C. saline solution
overnight after welding and then tested for tensile strength. The
breaking force of the laser weld was recorded using a tension
tester (Vitrodyne V1000, Liveco, VT). The standard load weight was
5000 g.
In groups 1 and 2, all samples were divided into 2 sets, one set
was tested for burst pressure and the other for tensile strength.
In group 3, 8 samples were tested for burst pressure and 9 for
tensile strength.
Results
Measurable objective parameters comparing each group were tensile
strength, burst pressure and total energy required to complete the
anastomosis were studied.
There were significant differences in burst pressures between the
grafts welded with the PSH stent and those using the liquid solder.
Higher burst pressures were observed in the groups 1 and 2 which
used the PSH stent. Some burst pressures were higher than 183 mmHg
and most of the measurements could not be recorded because our
pressure recorder was calibrated to a maximum pressure of 200 mmHg.
Three quarters of the measurements were above 200 mmHg in groups 1
and 2 (9/12). However, in group 3, the burst pressure ranged from
15.fwdarw.200 mmHg. Only 33.3% (3/9) in group 3 were over 200 mmHg.
83.3% (5/6) and 66.7% (4/6) of burst pressure were measured above
200 mmHg in group 1 and group 2, respectably.
The tensile strength of groups 1 and 2, with the PSH stent, were
420 (190 g/cm2 and 370.+-.170 g/cm2, respectively. In the group 3,
with the liquid solder, the average of tension was 240.+-.130
g/cm2. These values were significantly different (P<0.05).
The total energy consumption to complete the anastomosis in the
both of the PSH stent groups and solder group were significantly
different. More energy and time was spent at the anastomosis site
using the liquid solder (200.+-.45 J.) as compared with using the
PSH Stent (84.+-.38 J) for laser welding. But, there was no
significant difference between welding ureter to ureter and ureter
to heterograft using the PSH stent.
EXAMPLE 2
Sutureless End to End Ureteral and Heterograft Anastomosis--In Vivo
Study
Preparation of PSH Stent and Solder
25% Human serum albumin (MW: 66,500, Michigan Dept. of Public
Health, U.S. license No.99, MI) was filtered through an ultrafilter
membrane (YM 30, Amicom) using the ultrafiltration system (Model
8400, Amicom, MA) to concentrate it to 50% (W./V.). 10 mM ICG
(Sigma, I2633, MO) solution was filtered for sterilization (Gameo
25ES, Fisher) and added to 50% albumin at 1:100 by volume and mixed
well for 3 min. The mixture was air blow until the solvent
evaporated and became moldable. The moldable albumin was molded to
a hollow stent with outer diameter of 3.5 mm, inner diameter of 2.0
mm and 1.5 cm in length. The stent was stored at -4.degree. C. in
the dark until use. The procedure was performed using sterile
techniques.
The liquid solder was made of 50% (W./V.) albumin with 0.1 mM ICG
that was made similar to the photothermal sensitive stent without
drying procedures. The solder was stored in a 1 ml syringe at
-4.degree. C. in the dark until use.
Elastin Based Heterograft
The elastin based heterograft was processed from freshly harvested
porcine carotid arteries. The vessels were decellularized and
digested by 1% triton-X 100, DNase and collagenase. The final
product was composed of elastin at lumen surface and collagen on
the outer surface, and each graft was 6 cm in length, 3-4 mm in
inside diameter and 1 mm thick.
Laser System
Laser treatments were performed with a diode laser module (Diomed
Limited, Cambridge, UK) coupled to a quartz silica non-contact
fiber optic (600 .mu.m diameter). The laser system consists of a
phased array of gallium-aluminum-arsenide semiconductor diodes, and
the major wavelength output of the diode laser is 808 nm. In aiming
beam allow the operator to visualize the spot size of the laser
during activation. The spot diameter was .about.1 mm at a distance
of .about.2 mm. Laser power was measured and recorded at the out of
the optic fiber with a built-in laser meter monitor. The maximum
diode power output is 25 W. The laser was used in continuous wave
mode with 1 W output.
Twelve domestic female swine, weight 30-40 lbs., were studied in
this project. Five pigs were used for acute experiments and seven
were used for chronic experiments. Our surgical protocol followed
guidelines for the care and use of the laboratory animals and was
approved by the Animal Care and Use Committee of Oregon Health
Sciences University.
The animal was sedated with an IM injection of Telazol 1.5 ml
followed by general endotracheal anesthesia, using 1-2% Halothane
inhalant. Heart rate and oxygen saturation was monitored during the
surgery. The anesthetized pig was positioned supine, and shaved and
prepped in a sterile fashion. The paramedian retroperitoneal
approach was made from fourth nipple to below the last nipple.
In the acute group (N=5), 6-8 cm of the mid-segment of both ureters
were exposed and mobilized in an atraumatic manner, and 3-4 cm were
resected. On the right side, two PSH stents were placed into the
elastin tubular heterograft on each end with a 4.8 Fr..times.18 cm
double J ureteral stent inserted through the PSH hollow stent and
graft (Circon Surgitek, CA). The double J was placed through free
ureteral stumps into renal pelvis above and the bladder below. Then
the ureteral stump was pulled over the PSH stent to approximate
with the graft. Laser tissue welding was then done on the proximal
anastomosis followed by the distal one. On the left side, the
ureter was reconstructed with the graft without the PSH stent. The
liquid solder was applied in a thin coat on the seam before laser
irradiation. The solder covered approximately 1 mm on each side of
the anastomosis. The ureter ends and heterografts were spatulated
for the anastomosis. One hour after laser welding, retrograde
ureterography was preformed, then the animal was sacrificed and the
specimen was harvested and tested for tensile strength (Vitrodyna
1000, Liveco, VT).
In the chronic group (N=7), only the right ureter was operated. Two
animals were used as controls in this group and end to end
ureterureterostomy was done using laser welding with the PSH stent.
Five animals were used to perform ureter to heterograft end to end
anastomosis using PSH stent and laser. A 12 Fr. urethral catheter
was placed through urethra output from bladder. The bladder and
abdominal incision were closed in a standard fashion using a
running 3-0 chromic suture after making sure no leakage or bleeding
was present at the anastomotic sites. The catheter was sutured to
the animal's perineal skin and cut short to allow chronic urine
drainage and was removed at 1 week after surgery.
The animal was maintained on antibiotics for 14 days (Ampicillin
and Getamycin). 1 animals were sacrificed at 1 week, 2 at 2 wk. and
2 at 4 wks. Abdominal X-ray, intravenous pyelography and retrograde
ureterography were performed before sacrificed. The double J was
removed after retrograde urography. Then ureter was harvested for
histology.
The tissue samples were immediately fixed in 10% formalin solution.
Then the specimens were embedded with paraffin wax and sliced.
Trichrome, VVG, Von Kossas, Actin and H & E staining were
performed to study collagen, elastin, calcification and smooth
muscle regeneration. Statistical comparisons of all groups within
each parameter were examined using single T-test.
Results
The acute experiments were performed in five animals, during which
both ureters were replaced partially by elastin based tubular
heterograft using the PSH stent on one side and albumin based
liquid solder on the other side. Each side had two anastomoses. The
table 1 compares the welding time, tensile strength and propensity
to leakage during the acute experiments. Welding time for ureter to
heterograft anastomosis was significantly (P<0.05) decreased in
the PSH stent group (67.+-.27 sec.) compared to the albumin solder
group (121.+-.38 sec.). Leakage at the anastomotic sites was
interrogated using retrograde ureterography. The liquid albumin
soldering had a 30% leak rate (3/10). In the PSH group, there were
no immediate leaks evident. No significant difference was found
between the both groups in immediate tensile strength.
In the chronic experiment group, one case failed due to anastomotic
site leak at one week of postoperatively. Radiographic examination
revealed varying degrees of stricture and hydroureteronephrosis in
both groups.
The gross and histological examination showed that a solid
construct remained the gap between of ureter and heterograft after
1 hour perfusion at the PSH stent laser welding. A sponge
construction was observed at liquid solder laser welding. Fibrous
tissue surrounding the heterograft and urothelia hyperplasia at
anastomosis site were observed at 4 weeks after surgery. At 2 weeks
postoperatively, the albumin of the PSH stent plug was degraded and
penetrated by fibroblasts. By 4 weeks, the albumin was
degraded.
EXAMPLE 3
Laser Fusion of Vascular Heterograft--Acute Study
After proper identification of the animal, anesthesia was induced
with Telazole 8 mg/Kg I/M. Isoflurane was given by face mask and
the animal was intubated with a size 5 F cuffed endotracheal tube.
An I/V was inserted into a vein on its right ear and 7000 units of
heparin was given I/V. A six centimeter longitudinal incision was
made in the midline of the neck with a #15 blade. Division of the
subcutaneous tissue, and fascia between the strap muscles up to the
trachea was done using the electrocautery. Next to the trachea on
the right side the carotid sheath was identified and the common
carotid artery was isolated. The artery was soaked in papaverin
solution for five minutes to relieve spasm. The heterograft was
washed in heparinized saline for 20 minutes. Vascular clamps were
applied on the right common carotid 6 cm apart and the intervening
vessel was cut and ends spatulated. A 3.5 mm (outer diameter)
albumin-ICG hollow bullet stent was inserted into the heterograft
and then was invaginated into the distal carotid stump. Two stay
sutures of 7-0 prolene were tied on opposite sides in order to keep
the two vessel approximated. Fifty percent albumin-ICG liquid
solder was squirted on to the approximated edges and 2 mm on each
side. The 805 nm diomed-25 pulsed surgical laser was set at 5 Watts
with 0.1 sec pulse width and a 0.2 sec pulse interval. The edges
were lased circumferentially. A similar procedure was done on the
proximal end of the vessel. The vascular clamps were removed and
the graft was perfused for one hour. It took approximately 20
minutes for the bullet to dissolve. The specimen was explanted and
sent for histopathology. The animal was sacrificed.
EXAMPLE 4
Laser Fusion of Vascular Heterograft--Acute Study
After proper identification of the animal, anesthesia was induced
with Telazole 8 mg/Kg I/M. Isoflurane was given by face mask and
the animal was intubated with a size 5 F cuffed endotracheal tube.
An I/V was inserted into a vein on its right ear and 7000 units of
heparin was given I/V. A six centimeter longitudinal incision was
made in the midline of the neck with a #15 blade. Division of the
subcutaneous tissue, and fascia between the strap muscles up to the
trachea was done using the electrocautery. Next to the trachea on
the right side the carotid sheath was identified and the common
carotid artery was isolated. The artery was soaked in papaverin
solution for five minutes to relieve spasm. The heterograft was
washed in heparinized saline for 20 minutes. Vascular clamps were
applied on the right common carotid 6 cm apart and the intervening
vessel was cut and ends spatulated. A 3.5 mm (outer diameter)
albumin-ICG hollow bullet stent was inserted into the heterograft
and then was invaginated into the distal carotid stump. Two stay
sutures of 7-0 prolene were tied on opposite sides in order to keep
the two vessel approximated. Fifty percent albumin-ICG liquid
solder was squirted on to the approximated edges and 2 mm on each
side. The 805 nm diomed-25 pulsed surgical laser was set at 5 Watts
with 0.1 sec pulse width and a 0.1 sec pulse interval. The edges
were lased circumferentially. A similar procedure was done on the
proximal end of the vessel. The vascular clamps were removed and
the graft was perfused for three hour. It took approximately 20
minutes for the bullet to dissolve. The specimen was explanted and
sent for histopathology. The animal was sacrificed.
* * * * *